Rhythm of fetoplacental 11β-hydroxysteroid dehydrogenase type 2 - fetal protection from morning maternal glucocorticoids.

Excess glucocorticoids impact fetal health. Maternal glucocorticoids peak in early morning. Fetoplacental 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) inactivates cortisol to cortisone, protecting the fetus from high glucocorticoids. However, time-specific alterations of human fetoplacental 11β-HSD2 have not been studied.We hypothesized that fetoplacental 11β-HSD2 activity shows time-specific alteration and acute affective or anxiety disorders impact fetoplacental 11β-HSD2 activity.This study was observational.We investigated 78 pregnant European women undergoing amniocentesis (15.9 ± 0.9 weeks of gestation).Amniotic fluid was collected (8:00 - 16:30 hours) for analysis of fetoplacental 11β-HSD2 activity, using cortisol (F):cortisone (E) ratio in amniotic fluid, E/(E+F).Fetoplacental 11β-HSD2 rhythm and association with "acute affective or anxiety disorder" (patients with at least one of: a major depressive episode, specific phobia, panic disorder, generalized anxiety disorder, mixed anxiety and depressive disorder) and "acute anxiety disorder" (one of: panic disorder, generalized anxiety disorder, mixed anxiety, depressive disorder), assessed using Mini International Neuropsychiatric Interview (M.I.N.I.), were investigated.Activity of 11β-HSD2 correlated with time of amniocentesis, peaking in the morning (r=-0.398; p<0.001) and increased with acute affective or anxiety disorder (mean (M)=0.70 vs. M=0.74; p=0.037) and acute anxiety disorder (M=0.70 vs. M=0.75; p=0.016). These associations remained significant when controlling for confounders. 11β-HSD2 activity correlated negatively with pre-pregnancy BMI (r=-0.225; p=0.047).Our study indicates a time-specific alteration of fetoplacental 11β-HSD2 activity with peaking levels in the morning, demonstrating a mechanism of fetal protection from the morning maternal glucocorticoid surge.

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Authors: Eva Kathrin Lamadé, Ferdinand Hendlmeier, Stefan A Wudy, P D Dr Stephanie H Witt, Marcella Rietschel, Michaela Coenen, Maria Gilles, Michael Deuschle